Abstract
Programmed cell death ligand-1 immunohistochemical detection (PD-L1 IHC) is a putative predictor of response to PD-1/PD-L1-targeted checkpoint inhibitors. However, there is no gold standard assay in hepatocellular carcinoma (HCC). We evaluated 5 PD-L1 IHC assay platforms (E1LN3, 28-8, 22c3, SP263 and SP142) in 100 HCCs reporting PD-L1 expression in malignant (M) and tumour-infiltrating immune cells (TICs) and non-tumorous cirrhotic tissues (NTICs). We found substantial inter-assay heterogeneity in detecting PD-L1 expression in M (R2 = 0.080–0.921), TICs (Cohen’s κ = 0.175–0.396) and NTICs (κ = 0.004–0.505). Such diversity may impact on the reliability and reproducibility of PD-L1 IHC assays as a predictor of response to immune checkpoint inhibitors.
Highlights
Immune evasion through up-regulation of programmed cell death-1 (PD-1) pathway is a pivotal mechanism in the progression of hepatocellular carcinoma (HCC), a disease characterised by dismal prognosis and limited treatment options
Our observation mirrors the results generated in melanoma and non-small-cell lung cancer (NSCLC), where a number of companion diagnostic assays have evolved in parallel with the clinical development of PD-1/programmed cell death ligand-1 (PD-L1)-targeting immune checkpoint inhibitors (ICPIs).[8]
Unlike melanoma and NSCLC, HCC is unique for the presence of an immune cell-rich cirrhotic microenvironment, which adds a further layer of complexity to the classification of PD-L1 status
Summary
Immune evasion through up-regulation of programmed cell death-1 (PD-1) pathway is a pivotal mechanism in the progression of hepatocellular carcinoma (HCC), a disease characterised by dismal prognosis and limited treatment options. PD-L1 expression by immunohistochemistry (IHC) enriches for response to immune checkpoint inhibitors (ICPIs) in selected tumours.[2] its utility in HCC remains controversial. No recommendation can be made for an optimal PD-L1 IHC test in HCC, a tumour where PD-L1 expression predicts for adverse prognosis, but whose predictive role in defining an increased likelihood of response to ICPI remains unclear.[6] To address this issue, in Blueprint-HCC we performed a quantitative comparison of five antibody clones used for PD-L1 IHC testing in landmark trials of ICPI
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